Safety & tolerability 

The safety of SOLIQUA 100/33 was tested in 4 clinical studies and in a variety of patient types.1-6

  • IN THE LIXILAN-O PIVOTAL TRIAL, SOLIQUA 100/33 DEMONSTRATED SAFETY AND TOLERABILITY IN ADULT patients with t2dm uncontrolled on oads1

    Severe symptomatic hypoglycemia*
    (0 out of 469 patients)

    Hypoglycemia
    (38 out of 469 patients)

    • Hypoglycemia is the most common adverse event with insulin-containing therapy

    *Severe symptomatic hypoglycemia defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
    Hypoglycemia defined as self-monitored plasma glucose <54 mg/dL.

    Treatment-emergent adverse events (with frequency 5%)2

    Gastrointestinal adverse reactions occur more frequently at the beginning of therapy.1
    OAD, oral antidiabetic therapy.

  • IN THE LIXILAN-L PIVOTAL TRIAL, SOLIQUA 100/33 demonstrated safety and tolerability for PAtients uncontrolled on basal insulin1

    Incidence of hypoglycemia in adult patients with T2DM treated with SOLIQUA 100/33

    Severe symptomatic hypoglycemia*
    (4 out of 365 patients)

    Hypoglycemia
    (65 out of 365 patients)

    • Hypoglycemia is the most common adverse event with insulin-containing therapy

    *Severe symptomatic hypoglycemia defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
    Hypoglycemia defined as self-monitored plasma glucose <54 mg/dL.

    Treatment-emergent adverse events3

    Gastrointestinal adverse reactions occur more frequently at the beginning of therapy.1

    Discontinuation due to GI adverse events was 1.1% in this clinical trial3

  • IN THE LIXILAN-G PIVOTAL TRIAL, SOLIQUA 100/33 demonstrated safety and tolerability for patients uncontrolled on GLP-1 RA4

    Severe symptomatic hypoglycemia*
    (1 out of 255 patients)

    Hypoglycemia
    (24 out of 255 patients)

    • Hypoglycemia is the most common adverse event with insulin-containing therapy

    *Severe symptomatic hypoglycemia defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
    Hypoglycemia defined as self-monitored plasma glucose <54 mg/dL.

    Treatment-emergent adverse events (with frequency 3%)4

    Gastrointestinal adverse reactions occur more frequently at the beginning of therapy.1

  • SOLIQUA 100/33 demonstrated safety and TOLERABILITY for patients on premix insulin5

    Severe hypoglycemia*
    (1 out of 442 patients)

    Hypoglycemia†
    (28 out of 442 patients)

    • Hypoglycemia is the most common adverse event with insulin-containing therapy

    *Severe hypoglycemia defined as severe cognitive impairment requiring external assistance for recovery.2
    Hypoglycemia defined as self-monitored plasma glucose <54 mg/dL.

    Treatment-emergent adverse events6

    Gastrointestinal adverse reactions occur more frequently at the beginning of therapy.1

    Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.

  • Patients were 5x less likely to discontinue soliqua 100/33 vs the GLP-1 RA (lixisenatide)1

    0.9% of patients discontinued SOLIQUA 100/33 due to GI side effects vs 5.2% for the GLP-1 RA (lixisenatide)2

    • Hypoglycemia is the most common adverse event with insulin-containing therapy

    *Severe symptomatic hypoglycemia defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
    Hypoglycemia defined as self-monitored plasma glucose <54 mg/dL.

    Incidence of GI side effects in adult patients with T2DM uncontrolled on OADs2

    GI, gastrointestinal; OAD, oral antidiabetic therapy.

SOLIQUA 100/33 is a combination of a long-acting human insulin analog with a glucagon-like peptide-1 (GLP-1) receptor agonist (RA) indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Limitations of Use:

  • Has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
  • Not recommended for use in combination with any other product containing a GLP-1 receptor agonist.
  • Not for treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
  • Not recommended for use in patients with gastroparesis.
  • Has not been studied in combination with prandial insulin.

Important Safety Information

Important Safety Information for SOLIQUA 100/33 (insulin glargine and lixisenatide) injection 100 Units/mL and 33 mcg/mL

Contraindications

  • During episodes of hypoglycemia.
  • In patients with known serious hypersensitivity to insulin glargine, lixisenatide, or to any of the product components.

 

Warnings and Precautions

  • Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, life-threatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine.
    There have been reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.

 

  • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.

 

  • Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.

 

  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed.
    Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.

 

  • Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.

 

  • Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.

 

  • Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.

 

  • Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.

 

  • Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

 

  • Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.

 

Most Common Adverse Reactions

The most common adverse reactions reported in 5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache.
 

Drug Interactions

  • Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
  • The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta-blockers, clonidine, guanethidine, and reserpine).
  • The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
  • Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
  • Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.

 

Click here for full Prescribing Information.
Click here for information on Sharps Medical Waste Disposal.
Click here to learn more about Sanofi’s commitment to fighting counterfeit drugs.

References:

  1. SOLIQUA 100/33 Prescribing Information.
  2. Data on file. CSR 12404. Sanofi US.
  3. Data on file. CSR 12405. Sanofi US.
  4. Blonde L, Rosenstock J, Del Prato S, et al. Switching to iGlarLixi versus continuing daily or weekly GLP-1 RA in type 2 diabetes inadequately controlled
    by GLP-1 RA and oral antihyperglycemic therapy: the LixiLan-G randomized clinical trial. Diabetes Care. 2019;42(11):2108-2116. doi:10.2337/dc19-1357
  5. Rosenstock J, Emral R, Sauque-Reyna L, et al. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: clinical outcomes
    with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021;44(10):2361-2370. doi:10.2337/dc21-0393
  6. Data on file. LPS 15017. Sanofi US.

Important Safety Information

Important Safety Information for SOLIQUA 100/33 (insulin glargine and lixisenatide) injection 100 Units/mL and 33 mcg/mL

Contraindications

  • During episodes of hypoglycemia.
  • In patients with known serious hypersensitivity to insulin glargine, lixisenatide, or to any of the product components.

 

Warnings and Precautions

  • Anaphylaxis and Serious Hypersensitivity Reactions: In clinical trials of lixisenatide, there have been cases of anaphylaxis and other serious hypersensitivity reactions including angioedema. Severe, life-threatening, generalized allergic reactions, including anaphylaxis and angioedema, can occur with insulins, including insulin glargine.
    There have been reports of serious hypersensitivity reactions, including anaphylactic reactions and angioedema, in patients treated with SOLIQUA 100/33. If hypersensitivity reactions occur, discontinue SOLIQUA 100/33. Use caution in patients with a history of anaphylaxis or angioedema with another GLP-1 RA because it is unknown whether such patients will be predisposed to anaphylaxis.

 

  • Pancreatitis: Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 RAs. Cases of pancreatitis were reported in clinical trials of lixisenatide. After initiation of SOLIQUA 100/33, observe patients for signs and symptoms of pancreatitis (e.g., persistent severe abdominal pain, sometimes radiating to the back and which may be accompanied by vomiting). If pancreatitis is suspected, SOLIQUA 100/33 should promptly be discontinued. If pancreatitis is confirmed, restarting SOLIQUA 100/33 is not recommended and other antidiabetic therapies should be considered.

 

  • Never Share a SOLIQUA 100/33 SoloStar® Pen between Patients: Pen-sharing poses a risk for transmission of blood-borne pathogens, even if the needle is changed.

 

  • Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen: Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia. Changes should be made cautiously and the frequency of blood glucose monitoring should be increased. Adjustments in concomitant oral antidiabetic treatment may be needed.
    Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.

 

  • Medication Errors: SOLIQUA 100/33 contains two drugs. Do not administer more than 60 units of SOLIQUA 100/33, which may result in overdose of the lixisenatide component. Do not use other GLP-1 RAs. Accidental mix-ups between insulin products have been reported. Instruct patients to always check the label before administration. Do not withdraw SOLIQUA 100/33 from the pen with a syringe.

 

  • Hypoglycemia: Hypoglycemia is the most common adverse reaction associated with insulin-containing therapy, which may be life-threatening. Increase frequency of glucose monitoring with changes to: insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity, and in patients with renal or hepatic impairment and hypoglycemia unawareness.

 

  • Acute Kidney Injury: There have been reports of acute renal failure and worsening of chronic failure, which may sometimes require hemodialysis in patients treated with SOLIQUA 100/33. Some of these events were reported in patients without known underlying renal disease. Most reports occurred in patients who experienced nausea, vomiting, diarrhea, or dehydration; advise patients to take precautions to avoid fluid depletion. Monitor blood glucose and renal function in patients with renal impairment. SOLIQUA 100/33 is not recommended in patients with end-stage renal disease.

 

  • Immunogenicity: Patients may develop antibodies to insulin and lixisenatide. If there is worsening glycemic control or failure to achieve targeted glycemic control, significant injection site reactions or allergic reactions, then other antidiabetic therapy should be considered.

 

  • Hypokalemia: All insulin containing products can cause hypokalemia, which may be life-threatening. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

 

  • Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists: Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) and insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.

 

Most Common Adverse Reactions

The most common adverse reactions reported in 5% of patients treated with SOLIQUA 100/33 include hypoglycemia, nausea, nasopharyngitis, diarrhea, upper respiratory tract infection, and headache.
 

Drug Interactions

  • Certain drugs may affect glucose metabolism, requiring dose adjustment of SOLIQUA 100/33 and close monitoring of blood glucose.
  • The signs of hypoglycemia may be reduced or absent in patients taking anti-adrenergic drugs (eg, beta-blockers, clonidine, guanethidine, and reserpine).
  • The lixisenatide in SOLIQUA 100/33 delays gastric emptying, which may reduce the rate of absorption of orally administered medication with a narrow therapeutic ratio or that require careful clinical monitoring. If such medications are to be administered with food, do not co-administer with SOLIQUA 100/33.
  • Antibiotics, acetaminophen, or other medications that are dependent on threshold concentrations for efficacy, or where a delay in effect is undesirable, should be administered at least 1 hour before SOLIQUA 100/33 injection.
  • Oral contraceptives should be taken at least 1 hour before SOLIQUA 100/33 administration or 11 hours after.

 

Click here for full Prescribing Information.
Click here for information on Sharps Medical Waste Disposal.
Click here to learn more about Sanofi’s commitment to fighting counterfeit drugs.

References:

  1. SOLIQUA 100/33 Prescribing Information.
  2. Data on file. CSR 12404. Sanofi US.
  3. Data on file. CSR 12405. Sanofi US.
  4. Blonde L, Rosenstock J, Del Prato S, et al. Switching to iGlarLixi versus continuing daily or weekly GLP-1 RA in type 2 diabetes inadequately controlled
    by GLP-1 RA and oral antihyperglycemic therapy: the LixiLan-G randomized clinical trial. Diabetes Care. 2019;42(11):2108-2116. doi:10.2337/dc19-1357
  5. Rosenstock J, Emral R, Sauque-Reyna L, et al. Advancing therapy in suboptimally controlled basal insulin-treated type 2 diabetes: clinical outcomes
    with iGlarLixi versus premix BIAsp 30 in the SoliMix randomized controlled trial. Diabetes Care. 2021;44(10):2361-2370. doi:10.2337/dc21-0393
  6. Data on file. LPS 15017. Sanofi US.